Latent TGF-β binding proteins -3 and -4 : transcriptional control and extracellular matrix targeting

Extracellular matrix (ECM) is a complex network of various proteins and proteoglycans which provides tissues with structural strength and resilience. By harvesting signaling molecules like growth factors ECM has the capacity to control cellular functions including proliferation, differentiation and cell survival. Latent transforming growth factor β (TGF-β) binding proteins (LTBPs) associate fibrillar structures of the ECM and mediate the efficient secretion and ECM deposition of latent TGF-β. The current work was conducted to determine the regulatory regions of LTBP-3 and -4 genes to gain insight into their tissue-specific expression which also has impact on TGF-β biology. Furthermore, the current research aimed at defining the ECM targeting of the N-terminal variants of LTBP-4 (LTBP-4S and -4L), which is required to understand their functions in tissues and to gain insight into conditions in which TGF-β is activated. To characterize the regulatory regions of LTBP-3 and -4 genes in silico and functional promoter analysis techniques were employed. It was found that the expression of LTBP-4S and -4L are under control of two independent promoters. This finding was in accordance with the observed expression patterns of LTBP-4S and -4L in human tissues. All promoter regions characterized in this study were TATAless, GC-rich and highly conserved between human and mouse species. Putative binding sites for Sp1 and GATA family of transcription factors were recognized in all of these regulatory regions. It is possible that these transcription factors control the basal expression of LTBP-3 and -4 genes. Smad binding element was found within the LTBP-3 and -4S promoter regions, but it was not present in LTBP-4L promoter. Although this element important for TGF-β signaling was present in LTBP-4S promoter, TGF-β did not induce its transcriptional activity. LTBP-3 promoter activity and mRNA expression instead were stimulated by TGF-β1 in osteosarcoma cells. It was found that the stimulatory effect of TGF-β was mediated by Smad and Erk MAPK signaling pathways. The current work explored the ECM targeting of LTBP-4S and identified binding partners of this protein. It was found that the N-terminal end of LTBP-4S possesses fibronectin (FN) binding sites which are critical for its ECM targeting. FN deficient fibroblasts incorporated LTBP-4S into their ECM only after addition of exogenous FN. Furthermore, LTBP-4S was found to have heparin binding regions, of which the C-terminal binding site mediated fibroblast adhesion. Soluble heparin prevented the ECM association of LTBP-4S in fibroblast cultures. In the current work it was observed that there are significant differences in the secretion, processing and ECM targeting of LTBP-4S and -4L. Interestingly, it was observed that most of the secreted LTBP-4L was associated with latent TGF-β1, whereas LTBP-4S was mainly secreted as a free form from CHO cells. This thesis provides information on transcriptional regulation of LTBP-3 and -4 genes, which is required for the deeper understanding of their tissue-specific functions. Further, the current work elucidates the structural variability of LTBPs, which appears to have impact on secretion and ECM targeting of TGF-β. These findings may advance understanding the abnormal activation of TGF-β which is associated with connective tissue disorders and cancer.

Molecular biology and functions of epilysin (MMP-28)

Epilysin (MMP-28) is the most recently identified member of the matrix metalloproteinase (MMP) family of extracellular proteases. Together these enzymes are capable of degrading almost all components of the extracellular matrix (ECM) and are thus involved in important biological processes such as development, wound healing and immune functions, but also in pathological processes such as tumor invasion, metastasis and arthritis. MMPs do not act solely by degrading the ECM. They also regulate cell behavior by releasing growth factors and biologically active peptides from the ECM, by modulating cell surface receptors and adhesion molecules and by regulating the activity of many important mediators in inflammatory pathways. The aim of this study was to define the unique role of epilysin within the MMP-family, to elucidate how and when it is expressed and how its catalytic activity is regulated. To gain information on its essential functions and substrates, the specific aim was to characterize how epilysin affects the phenotype of epithelial cells, where it is biologically expressed. During the course of the study we found that the epilysin promoter contains a well conserved GT-box that is essential for the basic expression of this gene. Transcription factors Sp1 and Sp3 bind this sequence and could hence regulate both the basic and cell type and differentiation stage specific expression of epilysin. We cloned mouse epilysin cDNA and found that epilysin is well conserved between human and mouse genomes and that epilysin is glycosylated and activated by furin. Similarly to in human tissues, epilysin is normally expressed in a number of mouse tissues. The expression pattern differs from most other MMPs, which are expressed only in response to injury or inflammation and in pathological processes like cancer. These findings implicate that epilysin could be involved in tissue homeostasis, perhaps fine-tuning the phenotype of epithelial cells according to signals from the ECM. In view of these results, it was unexpected to find that epilysin can induce a stable epithelial to mesenchymal transition (EMT) when overexpressed in epithelial lung carcinoma cells. Transforming growth factor b (TGF-b) was recognized as a crucial mediator of this process, which was characterized by the loss of E-cadherin mediated cell-cell adhesion, elevated expression of gelatinase B and MT1-MMP and increased cell migration and invasion into collagen I gels. We also observed that epilysin is bound to the surface of epithelial cells and that this interaction is lost upon cell transformation and is susceptible to degradation by membrane type-1-MMP (MT1-MMP). The wide expression of epilysin under physiological conditions implicates that its effects on epithelial cell phenotype in vivo are not as dramatic as seen in our in vitro cell system. Nevertheless, current results indicate a possible interaction between epilysin and TGF-b also under physiological circumstances, where epilysin activity may not induce EMT but, instead, trigger less permanent changes in TGF-b signaling and cell motility. Epilysin may thus play an important role in TGF-b regulated events such as wound healing and inflammation, processes where involvement of epilysin has been indicated.

Co-Signaling by Neurotrophic Factors and the Extracellular Matrix for Axonal Growth and Neuronal Survival

Neurotrophic factors (NTFs) and the extracellular matrix (ECM) are important regulators of axonal growth and neuronal survival in mammalian nervous system. Understanding of the mechanisms of this regulation is crucial for the development of posttraumatic therapies and drug intervention in the injured nervous system. NTFs act as soluble, target-derived extracellular regulatory molecules for a wide range of physiological functions including axonal guidance and the regulation of programmed cell death in the nervous system. The ECM determines cell adhesion and regulates multiple physiological functions via short range cell-matrix interactions. The present work focuses on the mechanisms of the action of NTFs and the ECM on axonal growth and survival of cultured sensory neurons from dorsal root ganglia (DRG). We first examined signaling mechanisms of the action of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) on axonal growth. GDNF, neurturin (NRTN) and artemin (ART) but not persephin (PSPN) promoted axonal initiation in cultured DRG neurons from young adult mice. This effect required Src family kinase (SFK) activity. In neurons from GFRalpha2-deficient mice, NRTN did not significantly promote axonal initiation. GDNF and NRTN induced extensive lamellipodia formation on neuronal somata and growth cones. This study suggested that GDNF, NRTN and ARTN may serve as stimulators of nerve regeneration under posttraumatic conditions. Consequently we studied the convergence of signaling pathways induced by NTFs and the ECM molecule laminin in the intracellular signaling network that regulates axonal growth. We demonstrated that co-stimulation of DRG neurons with NTFs (GDNF, NRTN or nerve growth factor (NGF)) and laminin leads to axonal growth that requires activation of SFKs. A different, SFK-independent signaling pathway evoked axonal growth on laminin in the absence of the NTFs. In contrast, axonal branching was regulated by SFKs both in the presence and in the absence of NGF. We proposed and experimentally verified a Boolean model of the signaling network triggered by NTFs and laminin. Our results put forward an approach for predictable, Boolean logics-driven pharmacological manipulation of a complex signaling network. Finally we found that N-syndecan, the receptor for the ECM component HB-GAM was required for the survival of neonatal sensory neurons in vitro. We demonstrated massive cell death of cultured DRG neurons from mice deficient in the N-syndecan gene as compared to wild type controls. Importantly, this cell death could not be prevented by NGF the neurotrophin which activates multiple anti-apoptotic cascades in DRG neurons. The survival deficit was observed during first postnatal week. By contrast, DRG neurons from young adult N-syndecan knock-out mice exhibited normal survival. This study identifies a completely new syndecan-dependent type of signaling that regulates cell death in neurons.

Novel matrix metalloproteinases in intestinal inflammation and in cancer of the gastrointestinal tract

Matrix metalloproteinases (MMPs) comprise a family of 23 zinc-dependent human endopeptidases that can degrade virtually all components of the extracellular matrix (ECM). They are classified into eight subgroups according to their structure and into six subgroups based on their substrate-specificity. MMPs have been implicated in inflammation, tissue destruction, cell migration, arthritis, vascular remodeling, angiogenesis, and tumor growth and invasion. MMPs are inhibited by their natural inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Different MMPs function in the same tasks depending on the tissue or cancer subtype. I investigated the role of recently discovered MMPs, especially MMPs-19 and -26, in intestinal inflammation, in intestinal and cutaneous wound healing, and in intestinal cancer. Several MMPs and TIMPs were studied to determine their exact location at tissue level and to obtain information on possible functions of MMPs in such tissues and diseases as the healthy intestine, inflammatory bowel disease (IBD), neonatal necrotizing enterocolitis (NEC), pyoderma gangrenosum (PG), and colorectal as well as pancreatic cancers. In latent celiac disease (CD), I attempted to identify markers to predict later onset of CD in children and adolescents. The main methods used were immunohistochemistry, in situ hybridization, and Taqman RT-PCR. My results show that MMP-26 is important for re-epithelialization in intestinal and cutaneous wound healing. In colon and pancreatic cancers, MMP-26 seems to be a marker of invasive potential, although it is not itself expressed at the invasive front. MMP-21 is upregulated in pancreatic cancer and may be associated with tumor differentiation. MMPs-19 and -28 are associated with normal tissue turnover in the intestine, but they disappear in tumor progression as if they were protective markers . MMP-12 is an essential protease in intestinal inflammation and tissue destruction, as seen here in NEC and in previous CD studies. In patients with type 1 diabetes (T1D), MMPs-1, -3, and -12 were upregulated in the intestinal mucosa. Furthermore, MMP-7 was strongly elevated in NEC. In a model of aberrant wound repair, PG, MMPs-8, -9, and 10 and TNFα may promote ECM destruction, while absence of MMP-1 and MMP-26 from keratinocytes retards re-epithelialization. Based on my results, I suggest MMP-26 to be considered a putative marker for poor prognosis in pancreatic and colon cancer. However, since it functions differently in various tissues and tumor subtypes, this use cannot be generalized. Furthermore, MMP-26 is a beneficial marker for wound healing if expressed by migrating epithelial cells. MMP-12 expression in latent CD patients warrants research in a larger patient population to confirm its role as a specific marker for CD in pathologically indistinct cases. MMP-7 should be considered one of the most crucial proteases in NEC-associated tissue destruction; hence, specific inhibitors of this MMP are worth investigating. In PG, TNFα inhibitors are potential therapeutic agents, as shown already in clinical trials. In conclusion, studies of several MMPs in specific diseases and in healthy tissues are needed to elucidate their roles at the tissue level. MMPs and TIMPs are not exclusively destructive or reparative in tissues. They seem to function differently in different tissues. To identify selective MMP inhibitors, we must thoroughly understand the MMP profile (degradome) and their functions in various organs not to interfere with normal reparative functions during wound repair or beneficial host-response effects during cancer initiation and growth.

Hanle-Zeeman redistribution matrix. I. Classical theory expressions in the laboratory frame

Polarized scattering in spectral lines is governed by a 4; 4 matrix that describes how the Stokes vector is scattered and redistributed in frequency and direction. Here we develop the theory for this redistribution matrix in the presence of magnetic fields of arbitrary strength and direction. This general magnetic field case is called the Hanle- Zeeman regime, since it covers both of the partially overlapping weak- and strong- field regimes in which the Hanle and Zeeman effects dominate the scattering polarization. In this general regime, the angle-frequency correlations that describe the so-called partial frequency redistribution (PRD) are intimately coupled to the polarization properties. We develop the theory for the PRD redistribution matrix in this general case and explore its detailed mathematical properties and symmetries for the case of a J = 0 -> 1 -> 0 scattering transition, which can be treated in terms of time-dependent classical oscillator theory. It is shown how the redistribution matrix can be expressed as a linear superposition of coherent and noncoherent parts, each of which contain the magnetic redistribution functions that resemble the well- known Hummer- type functions. We also show how the classical theory can be extended to treat atomic and molecular scattering transitions for any combinations of quantum numbers.

Augustine and the functions of concupiscence

This study analyses Augustine s concept of concupiscentia, or evil desire (together with two cognate terms, libido and cupiditas) in the context of his entire oeuvre. By the aid of systematic analysis, the concept and its development is explored in four distinct ways. It is claimed that Augustine used the concept of concupiscentia for several theological purposes, and the task of the study is to represent these distinct functions, and their connections to Augustine s general theological and philosophical convictions. The study opens with a survey on terminology. A general overview of the occurrences of the negatively connoted words for desire in Latin literature precedes a corresponding examination of Augustine s own works. In this introductory chapter it is shown that, despite certain preferences in the uses of the words, a sufficient degree of synonymy reigns so as to allow an analysis of the concept without tightly discriminating between the terms. The theological functions of concupiscentia with its distinct contexts are analysed in separate chapters. The function of concupiscentia as a divine punishment is explored first (Ch 3). It is seen how Augustine links together concupiscentia and ideas about divine justice, and finally suggests that in the inordinate, psychologically experienced sexual desire, the original theological disobedience of Adam and Eve can be perceived. Augustine was criticized for this solution already in his own times, and the analysis of the function of concupiscentia as a divine punishment ends in a discussion on the critical response of punitive concupiscentia by Julian of Aeclanum. Augustine also attached to concupiscentia another central theological function by viewing evil desire as an inward originating cause for all external evil actions. In the study, this function is analysed by surveying two formally distinct images of evil desire, i.e. as the root (radix) of all evil, and as a threefold (triplex) matrix of evil actions (Ch 4). Both of these images were based on a single verse of the Bible (1 Jn 2, 16 and 1 Tim 6, 10). This function of concupiscentia was formed both parallel to, and in answer to, Manichaean insights into concupiscentia. Being familiar with the traditional philosophical discussions on the nature and therapy of emotions, Augustine situated concupiscentia also into this context. It is acknowledged that these philosophical traditions had an obvious impact into his way of explaining psychological processes in connection with concupiscentia. Not only did Augustine implicitly receive and exploit these traditions, but he also explicitly moulded and criticized them in connection with concupiscentia. Eventually, Augustine conceives the philosophical traditions of emotions as partly useful but also partly inadequate to deal with concupiscentia (Ch 5). The role of concupiscentia in connection to divine grace and Christian renewal is analysed in the final chapter of the study. Augustine s gradual development in internalizing the effects of concupiscentia also into the life of a baptized Christian are elucidated, as are the strong limitations and mitigations Augustine makes to the concept when attaching it into the life under grace (sub gratia). A crucial part in the development of this function is played by Augustine s changing interpretation of Rom 7, and the way concupiscentia appears in Augustine s readings of this text is therefore also analysed. As a result of the analysis of these four distinct functions and contexts of concupiscentia, it is concluded that Augustine s concept of concupiscentia is fairly tightly and coherently connected to his views of central theological importance. Especially the functions of concupiscentia as a punishment and the function of concupiscentia in Christian renewal were both tightly interwoven into Augustine s view of God s being and God s grace. The study shows the importance of reading Augustine s discussions on evil desire with a constant awareness of their role in their larger context, that is, of their function in each situation. The study warns against too simplistic and unifying readings of Augustine s concupiscentia, emphasizing the need to acknowledge both the necessitating, sinful aspects of concupiscentia, and the domesticated features of concupiscentia during Christian renewal.

The Structure and Functions of Hantavirus Nucleocapsid Protein

Hantaviruses, members of the genus Hantavirus in the Bunyaviridae family, are enveloped single-stranded RNA viruses with tri-segmented genome of negative polarity. In humans, hantaviruses cause two diseases, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), which vary in severity depending on the causative agent. Each hantavirus is carried by a specific rodent host and is transmitted to humans through excreta of infected rodents. The genome of hantaviruses encodes four structural proteins: the nucleocapsid protein (N), the glycoproteins (Gn and Gc), and the polymerase (L) and also the nonstructural protein (NSs). This thesis deals with the functional characterization of hantavirus N protein with regard to its structure. Structural studies of the N protein have progressed slowly and the crystal structure of the whole protein is still not available, therefore biochemical assays coupled with bioinformatical modeling proved essential for studying N protein structure and functions. Presumably, during RNA encapsidation, the N protein first forms intermediate trimers and then oligomers. First, we investigated the role of N-terminal domain in the N protein oligomerization. The results suggested that the N-terminal region of the N protein forms a coiled-coil, in which two antiparallel alpha helices interact via their hydrophobic seams. Hydrophobic residues L4, I11, L18, L25 and V32 in the first helix and L44, V51, L58 and L65 in the second helix were crucial for stabilizing the structure. The results were consistent with the head-to-head, tail-to-tail model for hantavirus N protein trimerization. We demonstrated that an intact coiled-coil structure of the N terminus is crucial for the oligomerization capacity of the N protein. We also added new details to the head-to-head, tail-to-tail model of trimerization by suggesting that the initial step is based on interaction(s) between intact intra-molecular coiled-coils of the monomers. We further analyzed the importance of charged aa residues located within the coiled-coil for the N protein oligomerization. To predict the interacting surfaces of the monomers we used an upgraded in silico model of the coiled-coil domain that was docked into a trimer. Next the predicted target residues were mutated. The results obtained using the mammalian two-hybrid assay suggested that conserved charged aa residues within the coiled-coil make a substantial contribution to the N protein oligomerization. This contribution probably involves the formation of interacting surfaces of the N monomers and also stabilization of the coiled-coil via intramolecular ionic bridging. We proposed that the tips of the coiled-coils are the first to come into direct contact and thus initiate tight packing of the three monomers into a compact structure. This was in agreement with the previous results showing that an increase in ionic strength abolished the interaction between N protein molecules. We also showed that residues having the strongest effect on the N protein oligomerization are not scattered randomly throughout the coiled-coil 3D model structure, but form clusters. Next we found evidence for the hantaviral N protein interaction with the cytoplasmic tail of the glycoprotein Gn. In order to study this interaction we used the GST pull-down assay in combination with mutagenesis technique. The results demonstrated that intact, properly folded zinc fingers of the Gn protein cytoplasmic tail as well as the middle domain of the N protein (that includes aa residues 80 248 and supposedly carries the RNA-binding domain) are essential for the interaction. Since hantaviruses do not have a matrix protein that mediates the packaging of the viral RNA in other negatve stranded viruses (NSRV), hantaviral RNPs should be involved in a direct interaction with the intraviral domains of the envelope-embedded glycoproteins. By showing the N-Gn interaction we provided the evidence for one of the crucial steps in the virus replication at which RNPs are directed to the site of the virus assembly. Finally we started analysis of the N protein RNA-binding region, which is supposedly located in the middle domain of the N protein molecule. We developed a model for the initial step of RNA-binding by the hantaviral N protein. We hypothesized that the hantaviral N protein possesses two secondary structure elements that initiate the RNA encapsidation. The results suggest that amino acid residues (172-176) presumably act as a hook to catch vRNA and that the positively charged interaction surface (aa residues 144-160) enhances the initial N-RNA interacation. In conclusion, we elucidated new functions of hantavirus N protein. Using in silico modeling we predicted the domain structure of the protein and using experimental techniques showed that each domain is responsible for executing certain function(s). We showed that intact N terminal coiled-coil domain is crucial for oligomerization and charged residues located on its surface form a interaction surface for the N monomers. The middle domain is essential for interaction with the cytoplasmic tail of the Gn protein and RNA binding.

Force constants and thermodynamic functions of iodine heptafluoride

Normal coordinate analysis of a molecule of the type XY7 (point group D5h) has been carried out using Wilson's FG, matrix method and the results have been utilized to calculate the force constants of IF7 from the available Raman and infrared data. Some of the assignments made previously by Lord and others have been revised and with the revised assignments the thermodynamic quantities of IF7 have been computed from 300°K to 1000°K under rigid rotator and harmonic oscillator approximation.

Functions of human papillomavirus E5 oncogene in epithelial cells and in the onset of cervical cancer

Human papillomaviruses (HPVs) are the causal agents of cervical cancer, which is the second most common cancer among women worldwide. Cellular transformation and carcinogenesis depend on the activities of viral E5, E6 and E7 proteins. Alterations in cell-cell contacts and in communication between epithelial cells take place during cervical carcinogenesis, leading to changes in cell morphology, increased cell motility and finally invasion. The aim of this thesis was to study genome-wide effects of the HPV type 16 (HPV-16) E5 protein on the expression of host cell messenger RNAs (mRNAs) and microRNAs by applying microarray technology. The results showed that the HPV-16 E5 protein alters several cellular pathways involved in cellular adhesion, motility and proliferation as well as in the extracellular matrix. The E5 protein was observed to enhance wound healing of epithelial cell monolayers by increasing cell motility in vivo. HPV-16 E5-induced alterations in the expression of cellular microRNAs and their target genes seem to favour increased proliferation and tumorigenesis. E5 was also shown to affect the expression of adherens junction proteins in HaCaT epithelial keratinocytes. In addition, a study of a membrane cytoskeletal cross-linker protein, ezrin, revealed that when activated, it localizes to adherens junctions. The results suggest that ezrin distribution to forming adherens junctions is due to Rac1 activity in epithelial cells. These studies reveal for the first time the holistic effects of HPV-16 E5 protein in promoting precancerous events in epithelial cells. The results contribute to identifyinging novel markers for cervical precancerous stages and to predicting disease behaviour.

Efficient algorithms for learning kernels from multiple similarity matrices with general convex loss functions

In this paper we consider the problem of learning an n × n kernel matrix from m(1) similarity matrices under general convex loss. Past research have extensively studied the m = 1 case and have derived several algorithms which require sophisticated techniques like ACCP, SOCP, etc. The existing algorithms do not apply if one uses arbitrary losses and often can not handle m > 1 case. We present several provably convergent iterative algorithms, where each iteration requires either an SVM or a Multiple Kernel Learning (MKL) solver for m > 1 case. One of the major contributions of the paper is to extend the well knownMirror Descent(MD) framework to handle Cartesian product of psd matrices. This novel extension leads to an algorithm, called EMKL, which solves the problem in O(m2 log n 2) iterations; in each iteration one solves an MKL involving m kernels and m eigen-decomposition of n × n matrices. By suitably defining a restriction on the objective function, a faster version of EMKL is proposed, called REKL,which avoids the eigen-decomposition. An alternative to both EMKL and REKL is also suggested which requires only an SVMsolver. Experimental results on real world protein data set involving several similarity matrices illustrate the efficacy of the proposed algorithms.

density matrix renormalization group study of polyacene

We study the nature of excited states of long polyacene oligomers within a Pariser-Parr-Pople (PPP) Hamiltonian using the Symmetrized Density Matrix Renormalization Group (SDMRG) technique. We find a crossover between the two-photon state and the lowest dipole allowed excited state as the system size is increased from tetracene to pentacene. The spin-gap is the smallest gap. We also study the equilibrium geome tries in the ground and excited states from bond orders and bond-bond correlation functions. We find that the Peierls instability in the ground state of polyacene is conditional both from energetics and structure factors computed froth correlation functions.

Quadratic Lyapunov functions for linear systems Journal

The paper deals with the existence of a quadratic Lyapunov function V = x′P(t)x for an exponentially stable linear system with varying coefficients described by the vector differential equation S0305004100044777_inline1 The derivative dV/dt is allowed to be strictly semi-(F) and the locus dV/dt = 0 does not contain any arc of the system trajectory. It is then shown that the coefficient matrix A(t) of the exponentially stable sy

Fracture analysis of concrete using singular fractal functions with lattice beam network and confirmation with acoustic emission study

In the present study singular fractal functions (SFF) were used to generate stress-strain plots for quasibrittle material like concrete and cement mortar and subsequently stress-strain plot of cement mortar obtained using SFF was used for modeling fracture process in concrete. The fracture surface of concrete is rough and irregular. The fracture surface of concrete is affected by the concrete's microstructure that is influenced by water cement ratio, grade of cement and type of aggregate 11-41. Also the macrostructural properties such as the size and shape of the specimen, the initial notch length and the rate of loading contribute to the shape of the fracture surface of concrete. It is known that concrete is a heterogeneous and quasi-brittle material containing micro-defects and its mechanical properties strongly relate to the presence of micro-pores and micro-cracks in concrete 11-41. The damage in concrete is believed to be mainly due to initiation and development of micro-defects with irregularity and fractal characteristics. However, repeated observations at various magnifications also reveal a variety of additional structures that fall between the `micro' and the `macro' and have not yet been described satisfactorily in a systematic manner [1-11,15-17]. The concept of singular fractal functions by Mosolov was used to generate stress-strain plot of cement concrete, cement mortar and subsequently the stress-strain plot of cement mortar was used in two-dimensional lattice model [28]. A two-dimensional lattice model was used to study concrete fracture by considering softening of matrix (cement mortar). The results obtained from simulations with lattice model show softening behavior of concrete and fairly agrees with the experimental results. The number of fractured elements are compared with the acoustic emission (AE) hits. The trend in the cumulative fractured beam elements in the lattice fracture simulation reasonably reflected the trend in the recorded AE measurements. In other words, the pattern in which AE hits were distributed around the notch has the same trend as that of the fractured elements around the notch which is in support of lattice model. (C) 2011 Elsevier Ltd. All rights reserved.

3D Acoustic Analysis Of Spherical Chamber Having Single Inlet And Multiple Outlet: An Impedance Matrix Approach

The transmission loss (TL) performance of spherical chambers having single inlet and multiple outlet is obtained analytically through modal expansion of acoustic field inside the spherical cavity in terms of the spherical Bessel functions and Legendre polynomials. The uniform piston driven model based upon the impedance [Z] matrix is used to characterize the multi-port spherical chamber. It is shown analytically that the [Z] parameters are independent of the azimuthal angle (phi) due to the axisymmetric shape of the sphere; rather, they depend only upon the polar angle (theta) and radius of the chamber R(0). Thus, the effects of relative polar angular location of the ports and number of outlet ports are investigated. The analytical results are shown to be in good agreement with the 3D FEA results, thereby validating the procedure suggested in this work.

3-D acoustic analysis of elliptical chamber mufflers having an end-inlet and a side-outlet: An impedance matrix approach

The acoustical behavior of an elliptical chamber muffler having an end-inlet and side-outlet port is analyzed semi-analytically. A uniform piston source is assumed to model the 3-D acoustic field in the elliptical chamber cavity. Towards this end, we consider the modal expansion of acoustic pressure field in the elliptical cavity in terms of angular and radial Mathieu functions, subjected to rigid wall condition, whereupon under the assumption of a point source, Green's function is obtained. On integrating this function over piston area of the side or end port and dividing it by piston area, one obtains the acoustic field, whence one can find the impedance matrix parameters characterizing the 2-port system. The acoustic performance of these configurations is evaluated in terms of transmission loss (TL). The analytical results thus obtained are compared with 3-D HA carried on a commercial software for certain muffler configurations. These show excellent agreement, thereby validating the 3-D semi-analytical piston driven model. The influence of the chamber length as well as the angular and axial location of the end and side ports on TL performance is also discussed, thus providing useful guidelines to the muffler designer. (c) 2011 Elsevier B.V. All rights reserved.